Single cell analysis of the developing and adult uveal tract reveals stromal and immune populations of relevance to the spectrum of uveal diseases

Thesis

The eye is a highly complex organ, in which miniscule deviations from baseline homeostasis can have profound impacts on vision. The uveal tract is a pigmented layer within the eye, with vital supportive roles for the function of the eye. Perturbations of the tissue microenvironment of the uvea occur in several pathologies of the eye such as inflammatory and degenerative eye diseases.

Single cell RNA sequencing has been transforming the understanding of cellular subtypes across organs, and the eye is no exception. However, the uveal tract has so far not been investigated in detail using single cell techniques either in development or in adult life. Here, I use single cell RNA sequencing to produce a single cell ‘atlas’ of the developing and adult uveal tract. I identify novel cell subtypes not previously documented within the uveal tract. Further, I identify subtypes of fibroblast within the uveal tract and demonstrate that there is heterogeneity of the fibroblast populations both within individual uveal regions, but also between the separate tissues that make up the uveal tract as a whole. Finally, I show that fibroblasts can be polarised towards specific phenotypes by exogenous signals, and demonstrate that fibroblast responses to some external mediators may play a role in pathologies of the uveal tract.

Authors: Reekie, IR

• DOI: 10.5287/ora-dmgxzg9e8
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: iris; uveitis; choroidal neovascularization; choroid; ciliary body; uvea
• Subjects: Choroid; Uveitis; Iris (Eye); Ciliary body; Eye